Platelets play an important role in the promotion of thrombus formation and blood coagulation, which takes place in the course of hemostasis, in which the bleeding caused by the breakage of blood vessels naturally stops. In humans, the platelets are released in the blood from megakaryocytes produced by differentiation from myeloid stem cells through megakaryocyte precursor cells.
A reduction in the number of platelets can be caused by thrombocytopenia, or by administration of anticancer drugs or irradiation with radioactive rays in treating cancers, which can result in serious consequences. However, no effective platelet-increasing agent has so far been discovered.
Heparin-binding secretory transforming factor gene (hst-1 gene) is a transforming gene, which has been isolated from the tissue of human stomach cancer [H. Sakamoto et al., Proc. Natl. Acad. Sci., U.S.A., 83, 3997 (1988)]. The gene product thereof shows some homology to fibroblast growth factor (FGF), one of cell growth factors, in structure and biological activity [T. Yoshida et al., Proc. Natl. Acad. Sci., U.S.A., 84, 7305 (1987) and K. Miyagawa et al., Oncogene, 3, 383 (1988)]. The hst-1 gene has been isolated not only from stomach cancer tissue, but also from the tissues of colon cancer, hepatic cancer and Kaposi sarcoma of patients suffering AIDS [T. Koda et al., Jpn. J. Cancer Res. (Gann), 78, 325 (1987), H. Nakagawa et al., Jpn. J. Cancer Res. (Gann), 78, 651 (1987), Y. Yuasa et al., Jpn. J. Cancer Res. (Gann), 78, 1035 (1987), and P. Delli Bovi et al., Cell, 50, 729 (1987)]. This gene has been clasified along with basic FGF, acidic FGF, int-2 gene, etc. as forming the FGF faimily. The gene isolated from the above-mentioned Kaposi sarcoma, which is identical to hst-1 is also called K-FGF.
The nucleotide sequence of the hst-1 gene has already been reported [M. Taira et al., Proc. Natl. Acad. Sci. U.S.A., 84, 2980 (1987), and T. Yoshida et al., Proc. Natl. Acad. Sci. U.S.A., 84, 7305 (1987)]. These reports provide the gene product deduced therefrom and the constituent amino acids of the hst-1 protein.
No effective platelet-increasing agent has so far been discovered, and the properties and biological activity of the hst-1 are unknown in many respects. It would be desirable to have an effective platelet-increasing agent. It would also be desirable to have such an agent that could readily be prepared.